The movie began with a narration over a black screen. Selene (Kate Beckinsale), a vampire "death-dealer," explains that vampires and Lycans (werewolves) have been at war for centuries. The war was suppose to end hundreds of years ago when Kraven, a vampire, killed the strongest of the Lycan, Lucian. Kraven rewarded for his actions with the leadership of the vampire clan. However, the war continued even without Lucian leading the Lycan. Vampire death-dealers were elite vampires who hunted down the Lycan. The screen opens to Selene perched on top of a balcony on a stormy night (as seen in the trailer).
Her inner monologue continues as she laments that the death-dealers were too successful, that there was only a handful of Lycan left. She is joined on other balconies by her teammates. They are stalking 2 Lycans who are walking on the streets below. The Lycan seem to be following a human (Scott Speedman from Felicity) into the subway stop. Selene and her teammates drop down from their rooftop positions (as seen in the trailer) to continue to follow the Lycan.
The Lycans noticed Selene and her team (very conspicuous in all that shiny black leather), and they pulled out their guns and opened fire. A huge gun battled erupts on the subway platform. Selene fires into the Lycan, but they do not seem to go down from her gunfire. However, the Lycan bullets hits one of her men, and he dies with light emitting from his eyes and mouth. Selene seemed shocked when she sees it happen. The other teammate was killed when one of the Lycan, a huge body builder type, transformed into his werewolf state and slashed him to death. Selene pursued the other wounded Lycan into the subway tunnels, and eventually ended in the sewers. She managed to finally kill him by emptying both of her guns into him. The transformed Lycan came up behind her, but she managed to elude him by wounding him with these flying ninja stars (as seen in the trailer). As she hides from the werewolf in the sewer, she hears a commotion above, which turned out to be a nest of Lycan. Their leader was lecturing them to be vigilant and focused if they want to beat the vampires on their own turf.
Selene makes it back to the vampire stronghold, which is a huge mansion. She reports to Kraven that there is a huge Lycan nest in town. She also showed him one of the Lycan's weapons she took off the one she killed. The bullets were filled with a special ultraviolet optic liquid, which is deadly to vampires. Kraven dismisses her claims in a condescending manner, telling her that most of the Lycans have been exterminated and they are not smart enough to build such a bullet. He is obviously very smitten by Selene, since he hits on her time and again throughout the film. Selene just shrugs him off. Kraven tells her to get ready for a big gathering that night, but Selene just goes to her room to review the surveillance photos from earlier. She figured out that the Lycan were following someone, she managed to find out the man's name is Michael Corvin and his address. Kraven comes into the room and yells at her for ignoring his order to get ready for the party. She just ignores him to go after Michael.
The next scene takes place inside a dirty medical room of some kind. You see two people hanging off the ground by their arms. A man wearing a pair of glasses and a bloody apron comes in and extract some blood from one of the hanging men. He mixes it into a beaker, and seem to be disappointed at the results. The Lycan leader from earlier comes in and ask about the results, and the medical Lycan (I'll refer to him as the doctor) just shake his head. Just then, the body builder Lycan Selene wounded came back. The ninja stars Selene threw were still embedded into his body. The Lycan leader asked whether he got Michael, and the body builder says no. They decide to make another try.
Selene breaks into Michael's apartment. While she looks around, Michael comes back from work (he is a doctor). Selene grabs him by the neck and slam him against the wall.
She asks him why the Lycan are after him, but he seems to be completely in the dark. The ceiling suddenly start to shake as the Lycan land on top of it. Selene and Michael makes a run for it as the Lycan burst into the apartment. Michael makes it to the elevator and closes it before Selene could catch up to him. She is now trapped at the end of the corridor as the Lycan closes in. To escape, she fires at the floor around her in a circle (as seen in the trailer) until the floor gives way. Meanwhile, Michael rides the elevator down. As the doors open, he comes face to face with the Lycan leader. Just then Selene makes it down the stairs and open fire on the Lycan leader. She hits him several times and he stumbles into Michael. He bites Michael on the neck while they are still on the floor. Selene comes over and grabs Michael. The Lycan leader spits the Michael's blood into a container. Selene and Michael jump into her car and drive away at top speed. The Lycan leader uses his powers to push the bullets out of his body. After he heals, he runs after the car at a fantastic speed and catches up to them. He jumps on top of the roof and pushes a blade hidden in his sleeve into the car. He manages to stab Selene in the shoulder. Selene slams the breaks and the Lycan gets thrown off by the momentum. She drives straight at him and rams him with the car. The Lycan lands nimbly on his feet as if nothing happened.
Michael tries to treat Selene's bleeding shoulder but she won't let him. Soon she passes out from the blood loss and loses control of the car. The car flips into the river. Michael saves Selene and uses a piece of clothes to bandage her wound. By now, he is feeling the effects of his wounds, and he falls unconscious by Selene. She is the first to wake up, and she takes Michael back to the Vampire Manor. While Selene watches the sleeping Michael, a blond female vampire comes in to inform Selene that Kraven wants to see her. She says she'll watch over Michael. Selene goes to meet a very mad Kraven. He scream at her for bring a human into their home. He seems enraged with jealousy and accuses her of being infatuated with Michael. The blond vampire is looking over Michael. She finds the bite mark on his neck. She vamps out (eyes turn violet/blue, fangs visible) and jumps onto the ceiling while hissing (as seen in the trailer). Michael wakes up and is shocked to see the vampire. He jumps out the window and runs from the manor. Kraven and Selene comes in to discover his escape. Kraven slaps Selene for her behavior. He then stalks out of the room.
Selene takes her frustrations out at the practice range. While there, the vampire weapons expert shows her a new weapon, bullets filled with silver nitrate. They would go straight into the bloodstream, so that Lycans would die much faster from it than the traditional silver rounds they used to use. Selene starts to suspect the circumstances which led to Kraven taking over the vampire clan. She investigates and realized that the Lycan leader she fought was Lucian. At the same time, we see Kraven in a secret meeting with Lucian. Lucian tells Kraven that everything was going to plan, and he needs to relax. Selene decided she needed to take extreme measures. She decided to break the covenant (the ruling law of the vampire race) by waking up her mentor Viktor, one of the elder vampires, from his hibernation. Apparently the covenant states that one elder vampire rules the vampire race at any one time. The others hibernate, sort of in a state of death, in a chamber within the manor. It was time for one of them, Marcus to awake, not Viktor. Selene used her own blood to begin the awaking process. She then races off to find Michael.
After being inactive for so long Viktor looks like a living rotting corpse. He has many tubes feeding blood into his system to help him regenerate. He summons Kraven to get an update on what has been happening. Kraven portrays Selene as being paranoid, and that she broke the covenant to awake Viktor a century too early. The current ruling elder, Amelia, was originally going to come to awaken Marcus. A security team was sent by Kraven to pick her up at the train station. In the mean time Michael goes to his hospital for treatment. He is starting to feel the effects of the bite, as he experiences memory flashbacks that are not his own. Selene locates him and takes him to a vampire hideout. She looks in the cabinet for some blood packs. She explains that vampires own one of the largest medical research companies in the world, and that they had perfected cloned blood. The company financed their lifestyles. She tells him that those flashbacks are Lucian's memories. He passed them to Michael when he bit him. Michael asks why Selene hates Lycans so much. She recounts how the werewolves killed her entire family one night. They were going to kill her too, but Viktor saved her. She was turned by Viktor so that she would have the strength to avenge her family. She tells Michael he would be safe if he stayed there, but he wants to go with her. She kisses him, but it was only a distraction as she handcuffed him a chair. She then sets off to seek guidance from Viktor.
Back in the Lycan hideout, Lucian hands the blood sample to the doctor. He performs the same test as earlier, and seem to be excited by the results. We see the Lycan troops arming themselves to the teeth in preparation for something. Selene walks back into the manor as all eyes fall upon her. She ignores the stares and walks purposely toward Viktor's chamber. Halfway she is grabbed by Kraven. He says that she has violated the ancient covenant, and that if she wants to avoid punishment she will do exactly as he says. Selene just knocks Kraven down and walks to the chamber. She explains to Viktor that Lucian is alive. She fears that he is plotting something and that Michael may be the key. Viktor sadly states that while her intentions were good she has no proof of Kraven's duplicity. And while he loves her as a daughter, she must be judged for breaking the covenant. She is taking away and locked in her room to await Amelia and the council's arrival for judgment. Kraven tells the guards to watch over his "future queen." The blond vampire hears this and helps Selene escape. When Selene asks why she is helping her, she said she was helping herself. Apparently she is attracted to Kraven.
As Amelia's train pulls into the station, Kraven's security team waits outside. They do nothing as a transformed Lycan group ambushes the convoy and slaughters Amelia and the council. Blood was extracted from the dying Amelia by the Lycan group. Another Lycan team heads to the vampire hideout where Michael is. Selene gets there first and holds off the Lycan team while Michael escapes through the window. But the team was just a distraction as Michael is grabbed outside and driven away. Selene did manage to capture the doctor and brought him back to Viktor as proof of Kraven's deceit. The doctor confesses the Lucian's plan. A person cannot be bitten both by vampires and Lycans because the viruses responsible for passing on either species powers do not mix. That person would die if they came into contact with one another. However, an ancient bloodline of the Corvinus house allows for such a union. What would result is a hybrid, half vampire and half Lycan, but stronger than both. Michael is part of that bloodline. Lucian was planning to inject himself with Michael's blood and the blood of a pure blood elder vampire (Amelia) so that he will be stronger than even Viktor. Just then the weapons expert from earlier burst in to announce that Amelia and the council were dead. The doctor laughs and exclaim that the reign of the vampires are at an end. Victor kills him with one punch (awesome scene), and orders a full assault on the Lycan stronghold in the sewers. He then tells Selene that if she wants redemption, she must kill Michael.
Meanwhile, Michael is held captive in the sewers. They extract more blood from him and Lucian puts it into his own body. Michael's flashbacks become clearer as his transformation deepens, and he suddenly understood how the war begun. The Lycan were slaves to the Vampires long ago. Lucian harbored no ill will though, and gladly guarded his masters during the day time when they were vulnerable. Eventually he fell in love with one of the vampires, Sonia. However, their marriage was seen as a threat by the vampires, for they were afraid of what their offspring would be. Lucian was thrown in prison and was forced to watch as Sonia was burned alive by the sun. Sonia was Viktor's daughter and he was the one who pronounced sentence on them. Kraven escaped from the manor to the sewers when his treachery was revealed. By then the vampire death-dealers had arrived and a full on war was on. Lucian mocks Kraven, saying that he may have to fight his own battle now. Kraven cowardly shoots Lucian in the back with the silver nitrate rounds.
Selene finds Michael and gets him out. As they near the exit they come face to face with an escaping Kraven. He hits Michael with the silver nitrate bullets, which starts to kill him because of the Lycan virus in his system. Kraven tries once again to get Selene to go with him, but she refuses. He mocks her and says that Viktor would never allow this union of a vampire and a lycan. He reveals that Viktor was the one that killed her family, not the Lycan. Sometimes he can't resist human blood. But Viktor couldn't kill Selene because she reminded him of his daughter and his guilt overwhelmed him. Kraven was about to finish Michael off when Lucian stabs him in the leg. Lucian tells Selene that if she wants to save Michael, she needs to bite him. Kraven fires at Lucian and finally kills him. He then limps away to escape. Selene bites Michael and began sucking his blood. She is thrown forcefully off him by Viktor. Viktor grabs Michael and throws him straight through a wall into a large cavernous room. Selene was stunned by her fall and laid on the ground. She confronts Viktor about his actions. Viktor says he loved his daughter, just like he loved Selene, but he had to do what was necessary to preserve their way of life, just as he must do once again. As he is about to kill Selene, a newly transformed hybrid Michael knocks him into the giant room. A fierce one-on-one fight occurs, with Michael using his claws and Viktor using a sword. As strong and fast as Michael is, Viktor eventually gains the upper hand. As he is strangling Michael, Selene picks up Viktor's sword and slashes his head in half. Selene walks over to Michael to help him up. The remaining Lycan look on as she leads him out of the room.
We hear Selene's narration as the movie cuts to Viktor's room in the manor. She says that both sides have suffered a terrible blow. The vampires will want retribution against her for the death of Viktor. Soon Marcus will be revived and the war will rage on. We see blood from the doctor's dead body pooling and flowing into the chamber where Marcus laid. The blood flows into Marcus's mouth. His eyes open and turn pure black. I guess the movie is setting up the sequel.